Open AccessStatin‐induced calcification in human mesenchymal stem cells is cell death related
Author(s) -
Kupcsik Laszlo,
Meurya Thomas,
Flury Matthias,
Stoddart Martin,
Alini Mauro
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00545.x
Subject(s) - pravastatin , lovastatin , mesenchymal stem cell , simvastatin , chemistry , alkaline phosphatase , statin , bone morphogenetic protein 2 , calcification , apoptosis , endocrinology , medicine , microbiology and biotechnology , biology , in vitro , biochemistry , cholesterol , enzyme
Statins are widely used in clinics to lower cholesterol levels. Recently, they have been shown to positively affect bone formation and bone mass in a rat model. The aim of this study was to investigate the effect of pravastatin, simvastatin and lovastatin on the osteoblastic differentiation of human mesenchymal stem cells (MSCs) in vitro . Cell number, alkaline phosphatase (ALP) activity, matrix mineralization and gene expression pattern were determined. Pravastatin did not affect cell differentiation. Simvastatin and lovastatin enhanced bone morphogenetic protein 2 (BMP‐2) mRNA levels. In contrast, ALP activity and mRNA levels were suppressed by statins, as well as the DNA content and cell activity (MTT). An increase in apoptotic events was observed at high concentrations of statins, along with high Ca‐45 incorporation. Lower concentrations of statins did not increase apoptotic staining, but also failed to induce calcification. When statin‐induced calcification did occur, the morphology of the deposits was very different from the conventional nodule formation; the calcium was laid down along the membranes of the rounded cells suggesting it was as a result of cell death. Our results indicate that statins are not able to differentiate human MSCs into osteoblasts and that high concentrations of statins (>1 μM) have a cytotoxic effect.